Multifunctional Iridium(III)–Platinum(IV) Conjugates as Potent Anticancer Theranostic Agents

In this article, we report IriPlatins 1–3,
a new class of heterobimetallic Ir(III)-Pt(IV) conjugates as multifunctional
potent anticancer theranostic agents. In the designed construction,
the octahedral Pt(IV) prodrug is tethered to the cancer cell targeting
biotin ligand through one of the axial sites and the other axial site
of Pt(IV) center is attached to multifunctional Ir(III) complexes
that possess organelle-targeting capabilities with excellent anticancer
and imaging properties. The conjugates preferentially accumulate within
the mitochondria of cancer cells, and subsequently, Pt(IV) is reduced
to Pt(II) species that concomitantly releases both the Ir(III) complex
and biotin from its axial sites. The IriPlatin conjugates
demonstrate potent anticancer activity in various 2D monolayer cancer
cells, including the cisplatin-resistant cells in the nanomolar concentrations
and 3D multicellular tumor spheroids. The mechanistic investigation
of conjugates suggests that the loss of MMP, generation of ROS, and
caspase-3-mediated apoptosis are responsible for cell death.